The dosing of drugs is carried out in a number of different ways in the to medical service today. Within health care more and more is focused on the possibility of dosing medical drugs as a powder directly to the airways and lungs of a patient by means of an inhaler in order to obtain an effective, quick and patient-friendly administration of such substances.
A dry powder inhaler, DPI, represents a device intended for administration of powder into the deep or upper lung airways by oral inhalation. With deep lung should be understood the peripheral lung and alveoli, where direct transport of active substance to the blood can take place. Particle sizes, to reach into the deep lung, should be in a range 0.5-3 μm and for a local lung a delivery in the range 3-5 μm. A larger grain size will easily stick in the mouth and throat, and a smaller grain size may accompany the expiration air out again.
To succeed with systemic delivery of medical powders to the deep lung by inhalation there are some criteria, which have to be fulfilled. The most important is a very high degree of de-agglomeration of the medical powder but also an exact dose is of great importance. This is not possible with dry powder inhalers of today without special arrangements as for example a so called spacer.
By means of a spacer the small grains are evenly distributed in a container from which the inhalation can take pace. Upon inhalation from the spacer the fine powder floating free in the air will effectively reach the alveoli of the lung. This method in principle has two drawbacks, firstly difficulties to control the amount of medicine emitted to the lung as an uncontrolled amount of powder sticks to the walls of the spacer and secondly difficulties in handling the relatively space demanding apparatus.
Powders for inhalers have a tendency of agglomerating, in other word to clod or to form small or larger lumps, which then have to be de-agglomerated. De-agglomeration is defined as breaking up agglomerated powder by introducing electrical, mechanical, or aerodynamic energy. Usually de-agglomeration is performed as a stage one during dosing and as a final stage two during the patient's inspiration through the DPI.
Inhaler devices normally use the force exerted by the patient's more or less normal inspiration effort for de-agglomerating the medical substance administered when inhaling in an effort to bring as much as possible of the active substance into the lungs. This often leads to inhaler de signs using high pressure drops, which will put the patient's lungpower to the test.
One major problem with some of the technique described above is to also obtain a low relative standard deviation (RSD) between doses with this type of technique due to lack of in line control possibilities in production mating it hard to be in compliance with regulatory demands.
As already noted for an optimum amount of substance to reach the alveoli, an administered powder dose should preferably have a grain size between 0.5 and 3 μm. Besides, the inspiration must take place in a calm way to decrease air speed and thereby reduce deposition in the upper respiratory tracts.
Technologies to de-agglomerate today include advanced mechanical and aerodynamic systems and combinations between electrical and mechanical filling systems that can be seen in for instance in U.S. Pat. No. 5,826,633. Further there are systems disclosed for dispersing aerosolized doses of medicaments, e.g. U.S. Pat. Nos. 5,775,320, 5,785,049, and 5,740,794. Furthermore, in our International Publications WO 00/0636 and WO 00/6235 principles for de-agglomeration and classification are disclosed.
The term electro-powder refers to a micronized medical powder presenting controlled electrostatic properties to be suitable for electrostatic administration in an inhaler device. Such an electro-powder provides possibilities for a better dosing from electrostatically operating equipment such as disclosed in our U.S. Pat. No. 6,089,227 as well as our Swedish Patents No. 9802648-7 and 9802649-5, which present excellent inhalation dosing performance.
The state of the art also discloses a number of solutions for depositing powder for dosing. U.S. Pat. No. 6,063,194 discloses a powder deposition apparatus for depositing grains on a substrate using an electrostatic chuck having one or more collection zones and using an optical detection for quantifying the amount of grains deposited. U.S. Pat. Nos. 5,714,007 and 6,007,630 disclose an apparatuses for electrostatically depositing a medicament powder upon predefined regions of a substrate, the substrates being used to fabricate suppositories, inhalants, tablet capsules and the like. In U.S. Pat. Nos. 5,699,649 and 5,960,609 are presented metering and packaging methods and devices for pharmaceuticals and drugs, the methods using electrostatic phototechnology to package microgram quantities of fine powders in discrete capsule and tablet form.
Devices of prior art technology does often not reach a sufficiently high degree of de-agglomeration and an exact dose is not well developed and leaves much to be desired when it comes to dosage conformity and lung deposition effectiveness of the medical substance. Therefore, there is still a demand of pre-fabricated high accuracy pre-metered doses to be loaded into an inhaler device, which then will ensure repeated exact doses to be given. The active dry powder then must possess a fine particle fraction, which guarantees its administration to a position within the lung of a patient where it will exert its expected effect.